The regulation of leucine biosynthesis, with emphasis on the first specific enzyme of the leucine pathway, alpha-isopropylmalate synthase, will be further investigated. Enteric bacteria (Salmonella typhimurium, Escherichia coli) as well as a simple eukaryote (the yeast Saccharomyces cerevisiae) will be used in order to establish evolutionary changes that might have occurred within this regulatory system. Special attention will be given to the recently discovered inactivation of yeast alpha-isopropylmalate synthase by coenzyme A.